2-210477778-G-A

Variant names:

• chr2-210477778-G-A
• rs17552879
• ENST00000430249.7:c.3+12G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001122633.3(CPS1):​c.-16+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.505 in 1,610,330 control chromosomes in the GnomAD database, including 209,952 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.44 (15891 hom., cov: 32)
  • Exomes 𝑓: 0.51 (194061 hom.)
• Consequence: CPS1 NM_001122633.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.39
• Publications: 13 publications found

Genes affected

CPS1 (HGNC:2323): (carbamoyl-phosphate synthase 1) The mitochondrial enzyme encoded by this gene catalyzes synthesis of carbamoyl phosphate from ammonia and bicarbonate. This reaction is the first committed step of the urea cycle, which is important in the removal of excess urea from cells. The encoded protein may also represent a core mitochondrial nucleoid protein. Three transcript variants encoding different isoforms have been found for this gene. The shortest isoform may not be localized to the mitochondrion. Mutations in this gene have been associated with carbamoyl phosphate synthetase deficiency, susceptibility to persistent pulmonary hypertension, and susceptibility to venoocclusive disease after bone marrow transplantation.[provided by RefSeq, May 2010]

LANCL1 (HGNC:6508): (LanC like glutathione S-transferase 1) This gene encodes a loosely associated peripheral membrane protein related to the LanC family of bacterial membrane-associated proteins involved in the biosynthesis of antimicrobial peptides. This protein may play a role as a peptide-modifying enzyme component in eukaryotic cells. Previously considered a member of the G-protein-coupled receptor superfamily, this protein is now in the LanC family. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2008]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-210477778-G-A is Benign according to our data. Variant chr2-210477778-G-A is described in ClinVar as Benign. ClinVar VariationId is 137026.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122633.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPS1	NM_001122633.3		c.-16+12G>A		intron	N/A	NP_001116105.2	P31327-1
	CPS1	NM_001369257.1		c.-136+12G>A		intron	N/A	NP_001356186.1	P31327-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CPS1	ENST00000430249.7	TSL:1	c.3+12G>A		intron	N/A	ENSP00000402608.2	P31327-3
	CPS1	ENST00000673510.1		c.-136+12G>A		intron	N/A	ENSP00000500537.1	P31327-1
	CPS1	ENST00000673630.1		c.-250+12G>A		intron	N/A	ENSP00000501073.1	P31327-1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66809 AN: 151888 Hom.: 15891 Cov.: 32

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.590

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.503

Gnomad OTH AF: 0.443

GnomAD2 exomes AF: 0.512 AC: 126630 AN: 247172 AF XY: 0.514

Gnomad AFR exome AF: 0.255

Gnomad AMR exome AF: 0.609

Gnomad ASJ exome AF: 0.427

Gnomad EAS exome AF: 0.628

Gnomad FIN exome AF: 0.480

Gnomad NFE exome AF: 0.493

Gnomad OTH exome AF: 0.487

GnomAD4 exome AF: 0.512 AC: 746332 AN: 1458324 Hom.: 194061 Cov.: 35 AF XY: 0.513 AC XY: 372321 AN XY: 725490

African (AFR) AF: 0.250 AC: 8347 AN: 33432

American (AMR) AF: 0.597 AC: 26606 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 11284 AN: 26082

East Asian (EAS) AF: 0.603 AC: 23890 AN: 39636

South Asian (SAS) AF: 0.586 AC: 50287 AN: 85872

European-Finnish (FIN) AF: 0.485 AC: 25821 AN: 53286

Middle Eastern (MID) AF: 0.381 AC: 2196 AN: 5760

European-Non Finnish (NFE) AF: 0.512 AC: 568493 AN: 1109444

Other (OTH) AF: 0.488 AC: 29408 AN: 60246

GnomAD4 genome AF: 0.440 AC: 66819 AN: 152006 Hom.: 15891 Cov.: 32 AF XY: 0.443 AC XY: 32933 AN XY: 74286

African (AFR) AF: 0.259 AC: 10728 AN: 41478

American (AMR) AF: 0.512 AC: 7819 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1469 AN: 3464

East Asian (EAS) AF: 0.610 AC: 3143 AN: 5154

South Asian (SAS) AF: 0.589 AC: 2834 AN: 4814

European-Finnish (FIN) AF: 0.479 AC: 5049 AN: 10548

Middle Eastern (MID) AF: 0.372 AC: 108 AN: 290

European-Non Finnish (NFE) AF: 0.503 AC: 34187 AN: 67960

Other (OTH) AF: 0.446 AC: 941 AN: 2110

Alfa AF: 0.465 Hom.: 4848

Bravo AF: 0.439

Asia WGS AF: 0.550 AC: 1910 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Congenital hyperammonemia, type I (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.24
DANN	Benign	0.40
PhyloP100		-1.4
PromoterAI		0.00060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs17552879; hg19: chr2-211342502; COSMIC: COSV52065402; COSMIC: COSV52065402;